rs4708431

Positions:

• chr6-168083405-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000646385.1(FRMD1):​c.-324-1543T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,178 control chromosomes in the GnomAD database, including 16,298 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (16298 hom., cov: 35)
• Consequence: FRMD1 ENST00000646385.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249

Genes affected

FRMD1 (HGNC:21240): (FERM domain containing 1) Predicted to be involved in positive regulation of hippo signaling. Predicted to be located in cytoskeleton. Predicted to be active in cytoplasmic side of apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD1	XM_011536138.2	c.11-4381T>C		intron_variant
FRMD1	XM_011536143.2	c.-37-4381T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD1	ENST00000644440.1	c.-11-4381T>C		intron_variant				A2
FRMD1	ENST00000646385.1	c.-324-1543T>C		intron_variant				P2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69351 AN: 152060 Hom.: 16291 Cov.: 35

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.424

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.456 AC: 69399 AN: 152178 Hom.: 16298 Cov.: 35 AF XY: 0.447 AC XY: 33254 AN XY: 74424

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.419

Alfa AF: 0.454 Hom.: 16844

Bravo AF: 0.460

Asia WGS AF: 0.226 AC: 792 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4708431; hg19: chr6-168484085;